Cancer Science最新文献_第3页

NOL7 Inhibits Ovarian Cancer Progression and Suppresses Angiogenesis by Stabilizing GADD45A to Deactivate STAT3. NOL7通过稳定GADD45A使STAT3失活抑制卵巢癌进展和血管生成

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-11 DOI: 10.1111/cas.70358

Xinyu Xu, Jiayuan Wang, Meng Jiang, Ling Ouyang

{"title":"NOL7 Inhibits Ovarian Cancer Progression and Suppresses Angiogenesis by Stabilizing GADD45A to Deactivate STAT3.","authors":"Xinyu Xu, Jiayuan Wang, Meng Jiang, Ling Ouyang","doi":"10.1111/cas.70358","DOIUrl":"10.1111/cas.70358","url":null,"abstract":"Ovarian cancer is one of the most prevalent gynecologic malignancies worldwide. Dysregulated cell proliferation and angiogenesis are well-recognized to be involved in the pathogenesis of ovarian cancer. Nucleolar Protein 7 (NOL7), a novel RNA-binding protein, has been identified as a tumor suppressor and a key anti-angiogenetic factor. However, the function of NOL7 and its underlying molecular mechanisms in ovarian cancer remain unclear. In this study, we demonstrated that NOL7 expression was down-regulated in ovarian cancer tissues, and low NOL7 expression was associated with poorer prognosis in patients with ovarian cancer. Overexpression of NOL7 decreased cell viability, inhibited cell cycle entry and proliferation, and promoted apoptosis in OVCAR-3 and SKOV-3 cells. Additionally, NOL7 overexpression decreased VEGF-A level, increased TSP-1, and suppressed angiogenesis of human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of NOL7 in ovarian cancer cells enhanced cell proliferation and angiogenesis, while reducing apoptosis. In vivo experiments further confirmed that NOL7 overexpression inhibited tumor growth and angiogenesis. Mechanistic studies revealed that NOL7 could bind to the 3'UTR of growth arrest and DNA damage inducible alpha (GADD45A), and overexpression of NOL7 up-regulated GADD45A expression by stabilizing GADD45A mRNA in ovarian cancer cells. The anti-cancer effects of the NOL7/GADD45A were mediated by inhibiting the phosphorylation of STAT3 at Ser727. Collectively, our findings indicate that NOL7 functions as a tumor suppressor in ovarian cancer and provide a novel therapeutic target for the treatment of ovarian cancer.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1303-1321"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147436817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circ-0030167/IGF2BP1 Induces Mitophagy-Mediated Ferroptosis via HMOX1 mRNA Stabilization in Pancreatic Cancer. Circ-0030167/IGF2BP1通过HMOX1 mRNA稳定诱导有丝分裂介导的胰腺癌铁凋亡。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-07 DOI: 10.1111/cas.70356

Qun Zhao, Xihao Yao, Jingjing Lu, Qiyang Chen, Zhiwei Wang, Xiaohong Li, Yuhua Lu

{"title":"Circ-0030167/IGF2BP1 Induces Mitophagy-Mediated Ferroptosis via HMOX1 mRNA Stabilization in Pancreatic Cancer.","authors":"Qun Zhao, Xihao Yao, Jingjing Lu, Qiyang Chen, Zhiwei Wang, Xiaohong Li, Yuhua Lu","doi":"10.1111/cas.70356","DOIUrl":"10.1111/cas.70356","url":null,"abstract":"Pancreatic cancer (PC) represents a highly aggressive malignancy characterized by a 5 year survival rate of less than 12%. Recent investigations suggest that mitophagy may constitute a potential therapeutic target for PC. This study aims to elucidate the molecular mechanisms underlying circ-0030167's regulation of PC, extending our prior investigations. mRNA sequencing analysis demonstrated significant enrichment of mitophagy-related signaling pathways in PC cells overexpressing circ-0030167. Integrated analysis utilizing RNA-binding protein (RBP) databases identified IGF2BP1 as a binding partner, a finding corroborated by RNA pull-down assays, RNA immunoprecipitation (RIP) experiments, and fluorescence in situ hybridization (FISH) validation. Cell-derived xenograft (CDX) assays confirmed that circ-0030167 enhances IGF2BP1 protein stability. Subsequent bioinformatic analysis combined with mRNA-seq data revealed HMOX1 as a downstream target gene within the circ-0030167/IGF2BP1-mediated mitophagy pathway. Functional assays measuring ferroptosis-related parameters-cell viability, reactive oxygen species (ROS) levels, malondialdehyde (MDA) content, and Fe2+ concentration-established that the circ-0030167/IGF2BP1 axis modulates mitophagy-mediated ferroptosis through HMOX1. Furthermore, in vivo animal studies demonstrated that circ-0030167 overexpression markedly suppresses PC tumor growth. In conclusion, our findings identify the circ-0030167/IGF2BP1/HMOX1 axis as a critical regulatory factor targeting mitochondria-mediated ferroptosis, thereby presenting a novel therapeutic target for PC combination therapies.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1362-1379"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations. 伴有FGFR基因家族改变的idh野生型胶质母细胞瘤的临床和遗传景观。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-02-25 DOI: 10.1111/cas.70347

Yasuhito Kegoya, Yoshihiro Otani, Ryo Mizuta, Ryosuke Ikemachi, Mako Kamiura, Joji Ishida, Shinichi Toyooka, Daisuke Ennishi, Shuta Tomida, Shota Tanaka

{"title":"Clinical and Genetic Landscape of Glioblastoma, IDH-Wildtype With FGFR Gene Family Alterations.","authors":"Yasuhito Kegoya, Yoshihiro Otani, Ryo Mizuta, Ryosuke Ikemachi, Mako Kamiura, Joji Ishida, Shinichi Toyooka, Daisuke Ennishi, Shuta Tomida, Shota Tanaka","doi":"10.1111/cas.70347","DOIUrl":"10.1111/cas.70347","url":null,"abstract":"Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family-such as FGFR::TACC fusions and FGFR1 mutations-have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1455-1468"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematic Multiplatform Discovery of Methylation Markers Enables Non-Invasive Early Detection of Endometrial Cancer. 甲基化标记的系统多平台发现使子宫内膜癌的无创早期检测成为可能。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-07 DOI: 10.1111/cas.70346

Yan Cai, Shuchao Chen, Zhen Wu, Jinxia Guan, Jie Zhao, Jianwei Ye, Baochen Du, Xiaoliang Han, Tong Shu, Guangpeng Zhou, Hong Zheng

{"title":"Systematic Multiplatform Discovery of Methylation Markers Enables Non-Invasive Early Detection of Endometrial Cancer.","authors":"Yan Cai, Shuchao Chen, Zhen Wu, Jinxia Guan, Jie Zhao, Jianwei Ye, Baochen Du, Xiaoliang Han, Tong Shu, Guangpeng Zhou, Hong Zheng","doi":"10.1111/cas.70346","DOIUrl":"10.1111/cas.70346","url":null,"abstract":"Endometrial cancer, the most common gynecological malignancy with an annual increase of 1%-3%, lacks suitable noninvasive diagnostic tools, as current methods like hysteroscopy and biopsy are invasive and impractical for routine screening. We conducted a comprehensive, multilayered marker discovery workflow integrating whole-genome bisulfite sequencing and targeted methylation panels in tumor and control tissues, then prioritized and optimized candidates for detection in cervical exfoliated cells. Using a two-stage design, we built and tested a quantitative methylation-specific PCR (qMSP) model in ThinPrep Cytology Test (TCT) samples, with 148 samples for discovery/model construction and an independent cohort of 80 TCT samples for validation. We identified a three-gene methylation panel-ZNF626, GRIA4, and SPDYA-that demonstrated high accuracy for early endometrial cancer detection from cervical cytology. In the validation cohort, the model showed strong performance across menopausal subgroups: in premenopausal women, sensitivity was 90.91% and specificity for benign endometrial disease was 92.59%; in postmenopausal women, sensitivity and specificity were 96.55% and 84.62%, respectively. Notably, the approach achieved a 92.86% detection rate for stage I endometrial cancer. These results support a robust, noninvasive diagnostic strategy that leverages simple cervical cytology sampling to enable early detection, facilitate clinical decision-making, and potentially improve outcomes for patients at risk of endometrial cancer.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1412-1421"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting PRMTs Creates Vulnerability of DNA Double-Stand Break Repair Pathways, and Potentiates Chemotherapy Efficacy in TNBC. 靶向PRMTs使DNA双支架断裂修复通路易损性增强TNBC化疗疗效

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-09 DOI: 10.1111/cas.70338

Charlène Thiebaut, Sébastien Martinez, Ludivine Pruvost, Louisane Eve, Rania El-Botty, Laura Sourd, Elodie Montaudon, Ahmed Dahmani, Heloise Derrien, Stéphanie Sentis, Coralie Poulard, Elisabetta Marangoni, Olivier Trédan, Muriel Le Romancer

{"title":"Targeting PRMTs Creates Vulnerability of DNA Double-Stand Break Repair Pathways, and Potentiates Chemotherapy Efficacy in TNBC.","authors":"Charlène Thiebaut, Sébastien Martinez, Ludivine Pruvost, Louisane Eve, Rania El-Botty, Laura Sourd, Elodie Montaudon, Ahmed Dahmani, Heloise Derrien, Stéphanie Sentis, Coralie Poulard, Elisabetta Marangoni, Olivier Trédan, Muriel Le Romancer","doi":"10.1111/cas.70338","DOIUrl":"10.1111/cas.70338","url":null,"abstract":"Patients with triple-negative breast cancer (ER-, PR-, and HER2-) are routinely treated with chemotherapies that induce DNA damage. However, around 30% of patients display resistance, owing largely to increased DNA repair mechanisms, upregulated to allow cancer cells to escape such therapies. PRMT1 and PRMT5, the two main protein arginine methyltransferases, are involved in several biological pathways, including DNA repair signaling, where they contribute to ensuring DNA integrity. We then speculated that targeting their enzymatic activity may sensitize TNBC cells to chemotherapeutic agents inducing DNA double-strand breaks. Here, we showed that PRMT1 and PRMT5 are recruited to DNA double-strand breaks upon doxorubicin or carboplatin treatment, two chemotherapies currently used to treat TNBC patients, and are preferentially involved in the homologous recombination pathway. By combining PRMT inhibitors with doxorubicin or carboplatin, we increased DNA double-strand breaks and impaired TNBC cell proliferation and clonogenicity in vitro and sensitized patient-derived models of TNBC to carboplatin treatment. These preclinical data provide a rationale for the clinical evaluation of PRMT inhibitors as combinatorial agents to improve chemotherapy efficacy for TNBC patients.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1273-1285"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD8⁺ T Cell Infiltration Elicits Molecular Subtype-Biased Clinical Outcomes in Gastric Cancer Patients. CD8+ T细胞浸润引发胃癌患者分子亚型偏倚的临床结果

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-20 DOI: 10.1111/cas.70366

Zhen Ling, Jieti Wang, Yun Gu, Ziqiu Zhang, Fei Shao, Chao Lin, Hongyong He, Ruochen Li, Hao Liu, Jiejie Xu

{"title":"CD8+ T Cell Infiltration Elicits Molecular Subtype-Biased Clinical Outcomes in Gastric Cancer Patients.","authors":"Zhen Ling, Jieti Wang, Yun Gu, Ziqiu Zhang, Fei Shao, Chao Lin, Hongyong He, Ruochen Li, Hao Liu, Jiejie Xu","doi":"10.1111/cas.70366","DOIUrl":"10.1111/cas.70366","url":null,"abstract":"CD8+ T cell infiltration is essential for antitumor immunity across cancers while its clinical significance in gastric cancer (GC) remains unclear. This reflects molecular heterogeneity of GC, as defined by The Cancer Genome Atlas (TCGA) into four subtypes: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI), chromosomal instability (CIN), and genomically stable (GS), each with distinct immune features. We aimed to characterize distribution, clinical relevance, and immune associations of CD8+ T cell infiltration within this molecular framework. TCGA (n = 336) and Zhongshan Hospital (ZSHS, n = 455) cohorts were analyzed. CD8+ T cell infiltration and immune features were compared across TCGA subtypes. Prognostic and predictive significance of CD8+ T cells was evaluated in ZSHS cohort. CD8+ T cell infiltration was elevated in the EBV-positive and MSI subtypes (ZSHS: p = 0.026; TCGA: p < 0.001). In ZSHS cohort, high CD8+ T cell infiltration was associated with better overall survival (p = 0.040), particularly in the EBV-positive (p = 0.036) and CIN (p = 0.065) subtypes, but not in MSI (p = 0.440) or GS (p = 0.860). Notably, low CD8+ T infiltration predicted superior response to adjuvant chemotherapy in MSI patients (HR = 0.210, p = 0.022). Immune profiling revealed associations of CD8+ T cells with antigen presentation in EBV-positive, tertiary lymphoid structure signatures in CIN, and podoplanin+ cells in GS tumors, instead of neoantigen burden in MSI or pan-fibroblast TGFβ response signature in GS. CD8+ T cell infiltration demonstrates subtype-specific prognostic and therapeutic significance in GC-beneficial in EBV-positive and CIN tumors, and predictive of chemotherapy response in MSI with low infiltration, which accompanied by divergent immune features, reflecting heterogeneous immunological landscape of GC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1434-1445"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CALR/HIF-1α Positive Feedback Loop Drives CALR Upregulation to Promote EMT-Mediated Bladder Cancer Progression via ROS/AKT Axis. CALR/HIF-1α正反馈环通过ROS/AKT轴驱动CALR上调促进emt介导的膀胱癌进展

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-05 DOI: 10.1111/cas.70354

Xintao Tian, Yue Liu, Zhiyuan Mi, Ye Liang, Zhao Zhang, Xiaocheng Ma, Huiqing Jia, Yuxuan Cao, Zhijuan Liang, Shaonan Yang, Guofeng Ma, Haitao Niu

{"title":"CALR/HIF-1α Positive Feedback Loop Drives CALR Upregulation to Promote EMT-Mediated Bladder Cancer Progression via ROS/AKT Axis.","authors":"Xintao Tian, Yue Liu, Zhiyuan Mi, Ye Liang, Zhao Zhang, Xiaocheng Ma, Huiqing Jia, Yuxuan Cao, Zhijuan Liang, Shaonan Yang, Guofeng Ma, Haitao Niu","doi":"10.1111/cas.70354","DOIUrl":"10.1111/cas.70354","url":null,"abstract":"CALR mutation is a key driver of myeloproliferative neoplasms (MPN) and has become a critical biomarker in clinical diagnostics and therapy. However, its function and mechanisms in solid tumors, particularly bladder cancer (BLCA), remain unclear. This study demonstrates that CALR expression is significantly elevated in BLCA, closely associated with poor patient prognosis, and serves as a critical factor promoting tumor progression. Further investigation reveals that the high expression of CALR stems from a novel positive feedback loop with HIF-1α in the tumor microenvironment: CALR stabilizes HIF-1α protein by von Hippel-Lindau (VHL), while HIF-1α transcriptionally upregulates CALR expression, thereby self-sustaining its high expression levels in BLCA. Mechanistically, CALR promotes the epithelial-mesenchymal transition (EMT) process by inducing intracellular reactive oxygen species (ROS) accumulation and activating the AKT signaling pathway, ultimately driving EMT-associated tumor progression. Finally, we identify the natural small-molecule compound-Sinapine as a direct inhibitor of CALR for the first time. Both in vitro and in vivo experiments confirmed that targeted inhibition of CALR effectively suppresses BLCA growth. This study not only elucidates the mechanism by which CALR maintains high expression through the CALR/HIF-1α positive feedback loop and promotes malignant progression in BLCA but also provides a theoretical foundation for its potential use as a prognostic biomarker and therapeutic target.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1286-1302"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial Transfer in the Tumor Microenvironment. 肿瘤微环境中的线粒体转移。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-02-13 DOI: 10.1111/cas.70342

Ryo Omae, Takamasa Ishino, Yosuke Togashi

{"title":"Mitochondrial Transfer in the Tumor Microenvironment.","authors":"Ryo Omae, Takamasa Ishino, Yosuke Togashi","doi":"10.1111/cas.70342","DOIUrl":"10.1111/cas.70342","url":null,"abstract":"Mitochondria are not merely energy-producing organelles but also regulate metabolism, apoptosis, and inflammation. Recent studies have reported that mitochondria can be transferred between cells, and accumulating evidence suggests that this phenomenon is functionally relevant in the tumor context. Mitochondrial transfer is mediated by multiple routes such as tunneling nanotubes and extracellular vesicles. These pathways are regulated by Miro1/2, connexin 43, ICAM-1, VCAM-1, and intracellular reactive oxygen species. Within the tumor microenvironment, mitochondrial transfer from surrounding cells to tumor cells may serve as a mechanism by which tumor cells adapt to hostile metabolic conditions and evade therapeutic pressure. Furthermore, mitochondrial transfer from tumor cells to T cells in the tumor microenvironment reportedly impairs antitumor immunity. Based on these findings, novel therapeutic strategies targeting mitochondrial transfer are under investigation. Future challenges include the development of specific and safe methods to manipulate mitochondrial transfer in vivo. Understanding mitochondrial transfer and its regulation may offer new avenues to overcome resistance and improve cancer outcomes.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1189-1198"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic Profiling in Localized Prostate Cancer: Associations With Biochemical Recurrence and Response to Salvage Radiotherapy. 局部前列腺癌的基因组分析：与生化复发和补救性放疗反应的关系。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-03-18 DOI: 10.1111/cas.70367

Kenji Zennami, Tetsuya Takimoto, Takuhisa Nukaya, Makoto Sumitomo, Mayu Takeda, Eiji Sugihara, Hideyuki Saya, Ryoichi Shiroki

{"title":"Genomic Profiling in Localized Prostate Cancer: Associations With Biochemical Recurrence and Response to Salvage Radiotherapy.","authors":"Kenji Zennami, Tetsuya Takimoto, Takuhisa Nukaya, Makoto Sumitomo, Mayu Takeda, Eiji Sugihara, Hideyuki Saya, Ryoichi Shiroki","doi":"10.1111/cas.70367","DOIUrl":"10.1111/cas.70367","url":null,"abstract":"The clinical significance of comprehensive genomic profiling (CGP) has been established in metastatic castration-resistant prostate cancer (PC). However, the role of genomic profiling in localized PC remains unclear. In this exploratory study, we evaluated somatic genomic alterations in localized PC using an in-house CGP platform to examine their associations with biochemical recurrence (BCR) and recurrence-free survival (RFS) after radical prostatectomy. DNA extracted from surgical specimens of 314 patients with localized PC was analyzed for alterations in 164 cancer-related genes. Six genes (PTEN, BRCA2, POLD1, ERBB3, MYC, and SETD2) were more frequently altered in patients who developed BCR in exploratory analyses. Patients harboring alterations in any of these genes (n = 96) showed higher pathological T stage, increased BCR rates (27.1% vs. 6.4%), and inferior RFS compared with alteration-negative patients (n = 218; p < 0.001). In multivariate analysis, the presence of these alterations was independently associated with worse RFS. Among individual genes, BRCA2 alteration, and particularly BRCA2-SETD2 co-alteration, were associated with unfavorable outcomes, although the latter finding was based on a limited number of cases. In patients who developed BCR, alterations were associated with shorter PSA doubling time and poorer outcomes after salvage radiotherapy, particularly in margin-negative cases; however, these subgroup analyses were based on small numbers and should be interpreted as hypothesis-generating. These findings suggest that somatic genomic alterations identified at prostatectomy are associated with early recurrence in localized PC. Further validation in independent cohorts is required to determine whether genomic profiling may contribute to future risk stratification and management strategies.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1469-1480"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Overlooked Autoantibody Repertoire: Exploring the Biomarker Potential of Downregulated Autoantibodies in NSCLC. 被忽视的自身抗体库：探索NSCLC中下调自身抗体的生物标志物潜力。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-05-01 Epub Date: 2026-02-17 DOI: 10.1111/cas.70343

Yihao Liang, Hanke Ma, Wenke Sun, Ying Chen, Fengqi Chen, Yutong Li, Songyun Ouyang, Liping Dai

{"title":"The Overlooked Autoantibody Repertoire: Exploring the Biomarker Potential of Downregulated Autoantibodies in NSCLC.","authors":"Yihao Liang, Hanke Ma, Wenke Sun, Ying Chen, Fengqi Chen, Yutong Li, Songyun Ouyang, Liping Dai","doi":"10.1111/cas.70343","DOIUrl":"10.1111/cas.70343","url":null,"abstract":"Autoantibodies (AAbs) represent promising biomarkers in cancer. While most AAbs are elevated in cancer, a substantial subset is downregulated, and their diagnostic and prognostic potential remains largely unexplored. Here we used the HuProt protein microarray to identify downregulated AAbs in non-small cell lung cancer (NSCLC) serum. Indirect ELISA quantified serum levels in 781 samples. Ten machine learning algorithms were used to construct diagnostic models. An independent cohort of 353 NSCLC patients was used to assess prognostic value and develop a prognostic model. Six downregulated AAbs were identified, among which five AAbs (anti-HIST1H1B, anti-HIST1H1C, anti-DYDC2, anti-CAMKK2, and anti-GRPEL1) were significantly reduced in NSCLC. The gradient boosting machine (GBM) model showed the best performance for NSCLC and BPNs, with AUCs of 0.869 (95% CI: 0.833-0.905) in the training set and 0.813 (95% CI: 0.745-0.880) in the validation set. For early-stage NSCLC, the model achieved an AUC of 0.809 (95% CI: 0.729-0.890) in the validation set, with a sensitivity of 74.0% and specificity of 81.3%. Multivariate Cox regression identified four AAbs significantly associated with patient prognosis. A prognostic model integrating age and AAb levels demonstrated robust predictive performance for long-term survival (7-year AUC = 0.79). Bioinformatics analyses further supported the relevance of the corresponding genes/proteins of these AAbs to NSCLC outcomes. Overall, our findings demonstrate that downregulated AAbs possess significant diagnostic and prognostic value in NSCLC and may contribute to improved patient management and survival prediction.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":"1244-1259"},"PeriodicalIF":4.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0